Viral infections can give rise to a systemic decrease in the total number of lymphocytes in the blood, referred to as lymphopenia. Lymphopenia may affect the host adaptive immune responses and impact the clinical course of acute viral infections. Detailed knowledge on how viruses induce lymphopenia would provide valuable information into the pathogenesis of viral infections and potential therapeutic targeting. In this review, the current progress of viruses-induced lymphopenia is summarized and the potential mechanisms and factors involved are discussed.